Insulinoma induces a hyperinsulinemia-mediated decrease of GLUT2 and GLP1 receptor in normal pancreatic ß-cells.

There have been several clinical reports of transient postoperative hyperglycemia in patients with insulinoma, but the effect of insulinoma on normal ß-cells has not been investigated. We examined the glucose transporter 2 (GLUT2) and glucagon-like peptide 1 receptor (GLP1R) expression in normal pancreatic ß-cells of five patients with insulinoma and five patients with normal glucose tolerance (NGT) as controls. The positive rate of GLUT2-or GLP1R-positive islets in the nontumor area was calculated by the ratio with the analyzed islets. For functional in vitro analyses, q-PCR and Western blotting were performed after insulin loading on MIN6 cells. The expression rates of both GLUT2 and GLP1R were significantly lower in nontumor area islets of insulinoma patients than in patients with NGT (GLUT2: 31.6 ± 15.3% vs 95.9 ± 6.7%, p < 0.01, GLP1R: 66.8 ± 15.0% vs 96.7 ± 5.0%, p < 0.01). Exposure of MIN6 cells to high concentrations of insulin resulted in a significant decrease in GLUT2 protein for 12 h and GLP1R protein for 24 h (GLUT2; 1.00 ± 0.079 vs 0.81 ± 0.04. p = 0.02, GLP1R; 1.00 ± 0.10 vs 0.50 ± 0.24, p = 0.03) but not in those mRNAs. Our findings show that insulinoma is associated with the downregulation of GLUT2 and GLP1R expression in nontumor area islets. These phenomena may be caused by high levels of insulin.

Gamma radiation-induced thermoluminescence, trace element and paramagnetic defect of quartz from the Sambagawa metamorphic belt, Central Shikoku, Japan.

This study analyzes the Thermoluminescence (TL) emissions for five emission bands, trace element concentrations and defects in quartz grains extracted from metamorphic rocks and quartz veins in the Sambagawa metamorphic belt, central Shikoku. An emission of 500nm with 195, 245, and 320-325°C glow peaks are observed through the lowest to highest grade samples. A 450nm emission band with intense 195 and 245°C glow peaks and a 320-325°C shoulder peak is found in the higher grade samples. A 570nm emission band with a 170°C glow peak is observed in the samples derived from the lower grade zones. These characteristics of TL emissions of quartz suggest that they can be an indicator for the identification of rock derived from different metamorphic grades. The higher metamorphic grade samples with 450nm emission bands in particular show higher intensities of the E1' center. This relation indicates that the activation of the E1' center in higher metamorphic conditions possibly contributed to the 450nm emission band. Also, the 500nm emission band is generally observed in the samples with the signal intensities of the Aluminum hole center, suggesting that the center is the source of this emission band. We also observed that the lower metamorphic grade samples contain lower signal intensities of the Aluminum hole center, despite higher aluminum concentrations. This inconsistency indicates that the formation of interstitial aluminum ions cause local lattice distortion regions, where self-trapped excitons can be formed and presumably provide the 570nm emissions.

Influence of 1 year of androgen deprivation therapy on lipid and glucose metabolism and fat accumulation in Japanese patients with prostate cancer.

BACKGROUND: We prospectively examined influence of androgen deprivation therapy (ADT) on lipid and glucose metabolisms in Japanese patients with prostate cancer. METHODS: Patients with prostate cancer who were hormone-naive and scheduled to receive long-term ADT were recruited between 2011 and 2013. Body weight, abdominal circumference and blood testing associated with lipid and glucose metabolism were recorded every 3 months during 1 year of ADT. Computed tomography (CT) was performed to measure areas of subcutaneous and visceral fat before and after 1 year of ADT. ADT was limited to a luteinizing hormone-releasing hormone (LHRH) agonist with or without bicalutamide. RESULTS: Of 218 patients registered, data were available from 177 patients who completed 1 year of ADT. Of these, CT was performed before and after 1 year of ADT in 88 patients. Median age was 75 years (range, 49-85 years). Median PSA before ADT was 16.7 ng ml(-1) (range, 0.3-3316). Clinical stage was B (54.2%), C (23.2%) and D (20.9%). Mean increases in body weight and abdominal circumference after 1 year of ADT were 2.9 and 3.0%, respectively. Mean increases in total, low-density lipoprotein and high-density lipoprotein cholesterol and triglycerides were 10.6, 14.3, 7.8 and 16.2%, respectively. Mean increases in fasting blood sugar and hemoglobin A1c (HbA1c) were 3.9 and 2.7%, respectively. Lipid alterations were noted in patients without comorbidities, whereas changes in HbA1c were noted in patients with diabetes mellitus at baseline. These lipid and glucose alterations were prominent in the early ADT period. Both visceral and subcutaneous fat, as measured by CT, increased by >20%. The increase in subcutaneous fat was significantly greater than that in visceral fat (P=0.028). CONCLUSIONS: One year of ADT significantly changed lipid and glucose metabolism in Japanese patients with prostate cancer. Patient characteristics or comorbidities at baseline may be associated with ADT-induced metabolic changes.

Feasibility and efficacy of intraperitoneal docetaxel administration as salvage chemotherapy for malignant gynaecological ascites.

Ovarian and endometrial cancers diagnosed at advanced stages are often associated with malignant ascites. This study aimed to determine the safety, feasibility and efficacy of intraperitoneal (IP) docetaxel (TXT) for the treatment of ascites. A phase I study, including nine patients, was undertaken to determine the maximum tolerable dose. Efficacy was retrospectively assessed in 18 patients treated with 40-70 mg/m(2) IP TXT between 2005 and 2012. In a phase I study, the dose was safely escalated to a maximum of 70 mg/m(2), at which level no patients had grade -3 haematological adverse events. In a retrospective study of 18 patients, seven had an Eastern Cooperative Oncology Group performance status of 3; 16 had prior paclitaxel administration and two, with doses of 40 and 70 mg/m(2), experienced a serological response and a decrease in paracentesis. Thus, palliative treatment of recurrent OC should be further studied with 40 mg/m(2) among more patients, and 70 mg/m(2) could be evaluated for first-line IP chemotherapy.

Spontaneous haemorrhage into metastatic brain tumours after stereotactic radiosurgery using a linear accelerator.

OBJECTIVE: To determine the incidence and clinical characteristics of spontaneous haemorrhage into metastatic brain tumours after radiosurgery. METHODS: Intratumour haemorrhage rate, clinical features, and treatment were evaluated in 54 patients with 131 brain metastases of varying origin who were treated using linear accelerator radiosurgery. The marginal dose was maintained constant at 20 or 25 Gy, irrespective of tumour size. RESULTS: Haemorrhage was identified in 7.4% of the metastases (five tumours in four patients) before radiosurgery and in 18.5% (10 tumours in 10 patients) after radiosurgery. In three cases, haemorrhage into the tumour after radiosurgery was symptomatic. Half the haemorrhages occurred within one month of radiosurgery. The changes in tumour size observed at the time of haemorrhage were an increase in one tumour, no change in five, and a decrease in four. Haemorrhage into a tumour after radiosurgery was more likely to occur in female patients, in tumours with a larger volume on pretreatment neuroimaging, and in tumours treated with a larger number of isocentres or a higher maximum dose. Haemorrhagic features in the patients or their tumours on presurgical assessment were not disposing factors to haemorrhage after radiosurgery. CONCLUSIONS: When larger brain metastases are aggressively treated by radiosurgery, better local control may be attained but there may also be a higher risk of haemorrhage soon after the treatment.

Neoadjuvant therapy and bladder substitute for invasive bladder cancer: 20 years experience at Tohoku University.

BACKGROUND: Neobladder, using the intestine, was performed after neoadjuvant therapy and total cystectomy as a treatment for invasive bladder cancer. METHODS: Between January 1977 and April 1997, an ileocecal neobladder was used for 23 patients and a sigmoid neobladder was chosen for use in 32 patients. For the diagnosis of invasive bladder cancer and the evaluation of neoadjuvant therapy, we used whole-layer core biopsy (WLCB) of the bladder tumor and fine needle aspiration biopsy (FNAB) of pelvic lymph nodes after bipedal lymphography. For neoadjuvant therapy, two to four courses of internal iliac arterial infusion chemotherapy (IIA) were undertaken in 32 patients. Five patients were treated with IIA combined with 40 Gy irradiation to the pelvic space. RESULTS: Pretreatment WLCB revealed a tumor of stage T2b or greater in 10 patients. After neoadjuvant therapy, three patients were down-staged to pT0. In five patients, pretreatment FNAB revealed pelvic lymph node metastases that were not detected by computed tomography or magnetic resonance imaging. Fine needle aspiration biopsy post-neoadjuvant therapy revealed tumor stage N0 in all patients and lymph node dissection revealed pN0 in four patients. Of the five patients who received 40 Gy irradiation, none had any postoperative complications, such as intestinal fistula or urinary leakage. Four male patients (10%) had urethral recurrence, but all were successfully treated by transurethral resection. Two patients treated prior to 1985 experienced local recurrence. Neither was treated by neoadjuvant therapy. Eight patients who died after 1985 had metastatic cancer, but none had local recurrence. None of the patients who received a sigmoid neobladder required clean intermittent catheterization or had bilateral vesico-ureteral reflux. CONCLUSIONS: Neoadjuvant therapy seems to reduce local recurrence in invasive bladder cancer. The sigmoid colon may be suitable for neobladder.

An extrahepatic bile duct metastasis from a gallbladder cancer mimicking Mirizzi's syndrome.

We report a case of an extrahepatic bile duct metastasis from a gallbladder cancer that mimicked Mirizzi's syndrome on cholangiography. A 67-yr-old woman was admitted to our hospital with a diagnosis of acute calculous cholecystitis. As obstructive jaundice developed after the admission, percutaneous transhepatic biliary drainage was performed to ameliorate the jaundice and to evaluate the biliary system. Tube cholangiography revealed bile duct obstruction at the hepatic hilus, and extrinsic compression of the lateral aspect of the common hepatic duct, with nonvisualization of the gallbladder. No impacted cystic duct stone was visualized on CT or ultrasonography. Laparotomy revealed a gallbladder tumor as well as an extrahepatic bile duct tumor. We diagnosed that the latter was a metastasis from the gallbladder cancer, based on the histopathological features. This case is unique in that the extrahepatic bile duct metastasis obstructed both the common hepatic duct and the cystic duct, giving the appearance of Mirizzi's syndrome on cholangiography. Metastatic bile duct tumors that mimic Mirizzi's syndrome have not been previously reported. The presence of this condition should be suspected in patients with the cholangiographic features of Mirizzi's syndrome, when the CT or ultrasonographic findings fail to demonstrate an impacted cystic duct stone.

Characterization of a mutant of Lactococcus lactis with reduced membrane-bound ATPase activity under acidic conditions.

A mutant of Lactococcus lactis subsp. lactis C2 with reduced membrane-bound ATPase activity was characterized to clarify its acid sensitivity. The cytoplasmic pH of the mutant was measured in reference to the parental strain under various pH conditions. At low pH, the mutant could not maintain its cytoplasmic pH near neutral, and lost its viability faster than the parental strain. The ATPase activities of cells cultured under neutral and acidic conditions using pH-controlled jar fermentors were measured. The relative ATPase activity of the mutant at pH 7.0 was 42% of the parental strain. At pH 4.5, the parental strain showed an ATPase activity 2.8-fold higher than that at pH 7.0 while the level of increase in the mutant was only 1.6. Northern and Western blot analyses found that at pH 7.0 the transcriptional level and the amount of F1 beta subunit were similar in both strains, suggesting that the mutant has a defective ATPase structural gene. On the other hand, at pH 4.5 the transcriptional level and the amount of F1 beta subunit were found to be significantly higher in both strains than those at pH 7.0. From these results, it was suggested that the mutant has a normal regulation system for ATPase gene expression. It was concluded that the mutant is acid sensitive due to its inability to extrude protons out of the cell with defective ATPase under acidic conditions.

Effects of prostaglandin F2alpha and cisapride on small intestinal activity during the early postoperative period in humans.

The relationship between intestinal motor activity and the influence of prostaglandin F2alpha (PGF) and cisapride were investigated during the early postoperative period in 26 patients who underwent abdominal surgery. Records of intestinal motility were made using an infusion catheter. PGF, 0.4 microg/kg per minute, given intravenously over 60 min, and cisapride, 5 mg, given intraintestinally, were administered to 13 patients each, first immediately after the operation, and then after the migrating motor complexes (MMCs) had reappeared following a period of intestinal quiescence. The MMCs were reestablished within the first postoperative day. Both PGF and cisapride stimulated irregular, high-amplitude contractions; however, the MMCs reappeared following these induced contractions only if the drugs were administered just after the postoperative MMCs became evident. These prokinetic drugs did not affect gastrointestinal hormone concentrations, but induced contractile activity even in the early postoperative period. Although the findings of this study demonstrate that these drugs may be useful as prokinetic agents to promote recovery from postoperative ileus just after the reappearance of MMCs in the early postoperative period, their precise mode of action has not been established.

Patterns of intestinal motility recovery during the early stage following abdominal surgery: clinical and manometric study.

The purpose of this study was to evaluate the pattern of recovery of intestinal motility using manometric and clinical assessment in the postoperative ileus following abdominal surgery. We reviewed the charts of 18 patients who underwent partial colectomy for colon cancer (group A, without vagotomy) and compared them to those of 15 patients who underwent gastrectomy with truncal vagotomy and reconstruction by the Billroth I technique (group B, with vagotomy). A three-lumen catheter was inserted via the nose into the proximal jejunum for drainage of intestinal fluids and to record intestinal motility at laparotomy. The first appearance of a burst activity following a silent period and a migrating motor complex (MMC) was at 3.8 hours (mean) and 16.4 hours, respectively, in group A, and at 2.5 and 14.3 hours, respectively, in group B. The first audible bowel sounds and the time of feeling abdominal fullness and passage of flatus was at 34.8, 47.5, and 62.9 hours (group A), and at 43.0, 53.8, and 77.9 hours (group B), respectively. The peak volume of nasointestinal drainage was recorded at 16 to 24 hours in group A and 40 to 48 hours in group B (p < 0.05). As measured by manometric examination, an MMC reappeared within a few hours after surgery. Physiologic postoperative ileus was ended when MMCs extended throughout the gastrointestinal (GI) tract with forwarding GI fluids.

Resection of metastatic liver cancer in a patient with an anomalous intrahepatic portal system: a case report.

Resection of metastatic liver cancer in a patient with an anomalous intrahepatic portal system is presented. A 67-year-old man was referred to our hospital with a liver tumor. Percutaneous transhepatic portography demonstrated that the right anterior branch of the portal vein rose from the left portal vein with agenesis of the umbilical portion. Cholangiography disclosed obstruction of the right posterior segmental bile duct by the tumor. Barium enema demonstrated a Borrmann type II cancer in the sigmoid colon. Right hepatic lobectomy and high anterior resection of the colon were performed, and postoperative histologic examination confirmed that the liver tumor was metastatic adenocarcinoma of the colon. The ligamentum teres arose from the right anterior portal vein and separated the left medial segment from the right anterior portal segment of the liver. These anomalies led to the performance of right lobectomy instead of trisegmentectomy and the patient died 10 months later of hepatic recurrence. This case emphasizes the importance of delineating the hepatic vascular anatomy before liver resection and illustrates one of the pitfalls related to portal venous anomalies.

Carcinoma of the cystic duct protruding into the common bile duct: report of a case.

We report herein the case of 65-year-old man in whom a diagnosis of primary carcinoma of the cystic duct was made on the basis of Farrar's criteria. The patient was admitted with upper abdominal pain, and although there was no evidence of jaundice or a palpable mass, there was tenderness in his right upper quadrant. Carcinoma of the cystic duct was suspected on the basis of computed tomography and magnetic resonance imaging findings. Cholecystectomy with resection of the bile duct and lymph node resection was performed, and percutaneous transhepatic cholangiography revealed a filling defect in the common bile duct (CBD). The tumor was found to have arisen from the cystic duct and demonstrated papillary growth into the CBD intraluminally through the orifice of the cystic duct. Microscopically, the tumor was identified as papillary adenocarcinoma with invasion limited to the subserosal layer of the cystic duct. There were no signs of nodal metastasis.

[A case of lung cancer avoidable right pneumonectomy due to external and intraluminal irradiation therapy].

A 54-year-old man with squamous cell carcinoma of the lung resected after external and high dose rate intraluminal irradiation (HDRII) therapy is reported. Cancer existed in right lower bronchus, extended to bifurcation of upper broncus and truncus intermedius. The patient received external irradiation of 40 Gy and HDRII of 18 Gy (Iridium192 was used) simultaneously. Effectiveness of irradiation was remarkable, tumor disappeared in chest CT and bronchoscopy. Middle and lower lobectomy and bronchial wedge resection was performed. Histologically, cancer was not existed in second carinal portion, so curative resection was done. The result suggests that HDRII is effective therapy as preoperative adjuvant irradiation.

[Evaluation of effective neo-adjuvant chemotherapy (FLEP therapy) in the treatment of advanced gastric cancer].

Ten patients with non-resectable gastric cancer were subjected to a neo-adjuvant chemotherapy (FLEP therapy), consisting of 4 drugs (leucovorin and 5-FU i.v., CDDP and etoposide i.a.) combination therapy from August 1989 to April 1991. The response rate of this therapy with primary lesions, metastatic lymph-nodes (mainly paraaortic lymph nodes), metastatic liver tumor and peritoneal dissemination were 50, 50, 25 and 33%, respectively. Five cases underwent total gastrectomy. Pathological evaluation of these cases was Grade 1 or 2. Side effects were mainly gastrointestinal disturbances, namely stomatitis, nausea, vomiting and anorexia, along with bone marrow suppression. Performance status of these patients improved to a significant degree by the therapy. This therapy seemed to be effective in controlling paraaortic lymph-node metastasis. The advantage of i.a. delivery was investigated by Tc-MAA scintigraphy. The distribution of Tc-MAA after i.a. injection suggested that i.a. chemotherapy enhanced intraabdominal drug concentration. There is no established treatment for far advanced cases, so this therapy seems to be worth a try.